Migraine is a complex neurovascular disorder driven by central brainstem dysfunction and abnormal cortical excitability
Cortical Spreading Depression (CSD): Alterations in cortical neuronal excitability—often driven by shifts in ion dynamics ($\uparrow\text{Ca}^{++}$, $\uparrow\text{Glu}$, $\downarrow\text{Mg}^{++}$)—trigger a self-propagating wave of cellular depolarization across the cerebral cortex
. This process underlies the classic focal neurological visual, sensory, or motor deficits seen during a migraine aura . Trigeminovascular System (TGVS) Activation: CSD directly leads to the activation and sensitization of the TGVS
. Perivascular nerve terminals release vasoactive neuropeptides, causing neurogenic inflammation and local vasodilation . Central Sensitization: Sustained TGVS signaling heightens sensitivity within brainstem structures (such as the periaqueductal gray) and secondary thalamic neurons, converting vascular pulsation into the characteristic throbbing headache pain
.
Targeting TGVS pathways forms the cornerstone of acute and preventive pharmacological strategies.